title: Chronic inflammation in biomaterial-induced periprosthetic osteolysis: NF-κB as a therapeutic target.
abstract: Biomaterial-induced tissue responses in patients with total joint replacement are associated with the generation of wear particles, which may lead to chronic inflammation and local bone destruction (periprosthetic osteolysis). Inflammatory reactions associated with wear particles are mediated by several important signaling pathways, the most important of which involves the transcription factor NF-κB. NF-κB activation is essential for macrophage recruitment and maturation, as well as the production of pro-inflammatory cytokines and chemokines such as TNF-α, IL-1β, IL-6 and MCP1. In addition, NF-κB activation contributes to osteoclast differentiation and maturation via RANK/RANKL signaling, which increases bone destruction and reduces bone formation. Targeting individual downstream cytokines directly (such as TNF-α or IL-1β) may not effectively prevent wear particle induced osteolysis. A more logical upstream therapeutic approach may be provided by direct modulation of the core IκB/IKKα/β/NF-κB signaling pathway in the local environment. However, the timing, dose and strategy for administration should be considered. Suppression of chronic inflammation via inhibition of NF-κB activity in patients with malfunctioning joint replacements may be an effective strategy to mitigate wear particle induced periprosthetic osteolysis.
authors.affiliation: Department of Orthopaedic Surgery, Stanford University, Stanford, CA, USA.
authors.forename: Tzu-hua
authors.initials: TH
authors.lastname: Lin
authors.forename: Yasunobu
authors.initials: Y
authors.lastname: Tamaki
authors.forename: Jukka
authors.initials: J
authors.lastname: Pajarinen
authors.forename: Heather A
authors.initials: HA
authors.lastname: Waters
authors.forename: Deanna K
authors.initials: DK
authors.lastname: Woo
authors.forename: Zhenyu
authors.initials: Z
authors.lastname: Yao
authors.forename: Stuart B
authors.initials: SB
authors.lastname: Goodman
mesh_terms: D000818:Animals; D001672:Biocompatible Materials / Q000009:adverse effects*; D002908:Chronic Disease; D006801:Humans; D007249:Inflammation / Q000209:etiology*; D007595:Joint Prosthesis / Q000009:adverse effects*; D016328:NF-kappa B / Q000378:metabolism*; D010014:Osteolysis / Q000209:etiology* / Q000628:therapy*; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D001672:Biocompatible Materials; D016328:NF-kappa B
keywords: Biomaterials; Chronic inflammation; NF-κB; Periprosthetic osteolysis